The Roles Of Cyclin A2(CCNA2) In Modulating The Functions Of Placental Trophoblast

Aims:Pregnancy is a complex biological process,the research of which is the basis of the treatment for pregnancy-related diseases.Recurrent miscarriage(RM)is defined as two or more pregnancy losses until 24 weeks of gestation,which is a natural model for us to uncover the mystery of pregnancy.Cyclin A2(CCNA2)is widely involved in proliferation,differentiation,and invasion of normal and tumor cells.However,little is known about CCNA2’s functions in trophoblast,although it is highly expressed in the placenta.The aim of our research is to explore the functions of CCNA2 in trophoblast and the possible mechanisms.Content and Methods:We collected the first-trimester villi of idiopathic recurrent miscarriages and health controls to clarify the expression level of CCNA2.Meanwhile,we used the first-trimester chorionic villous explants and HTR-8/SVneo cell line as research models to do the loss-and gain-of-funcion researches of CCNA2.Results:Our study showed that CCNA2 was downregulated in trophoblast of idiopathic recurrent miscarriage first-trimester villi.We found that CCNA2 enhanced trophoblast migration,proliferation and suppressed their apoptosis.On the one hand,CCNA2 promotes trophoblast migration via the RhoA-ROCK signaling.On the other hand,CCNA2 increased trophoblast proliferation and inhibited their apoptosis via p53 pathway.In addition,the relationship between ROCK signaling and p53 pathway was found.Further mechanistic research attributed the regulatory function of CCNA2 on p53 pathway to the involvement of DNA damage.Conclusions:Our study revealed that CCNA2 regulates trophoblast migration,proliferation,and apoptosis via different but related mechanisms,providing a possible pathogenesis of recurrent miscarriage.